Since George Lamb couldn’t investigate his way out of a paper bag, I got in touch with Matt Bowden, the guy behind BZP, for a bit more of an in-depth commentary. If you never watched Can I Get High Legally?, now would be a good time to check it out. Matt is interviewed towards the end, but is barely given the chance to speak. Actually, he only agreed to speak to them on the condition that they mention his Aroma product and Club Stargate website, where you can earn money by getting your mates to buy stuff. I know since it’s the BBC that they couldn’t actually mention these things, but then why did they agree to it? That’s just not nice.

So, anyway, here’s what Matt has to say:

My points all simply come back to quoting proven research. Sure, BZP has risks. We analysed the risk after 10 million exposures in a country small enough that you can contact every hospital and A & D clinic to look for adverse events related to the ten million exposures (26 million pills consumed over 8.5 years) and learned that it was not causative in any reported deaths or significant lasting injuries and had not contributed to the burden on the alcohol and drug treatment industries. Nobody in the country had complained anywhere of addiction to the drug.

Nobody had ever been admitted to hospital or even presented at an emergency department who had followed the instructions on the packet and in every case where there was a hospital admission, the subject had well over the legal alcohol limit (for driving) as well. In some cases where seizures were reported they were up to 15 times over the alcohol limit! In other words they were in very poor shape even without the BZP.

There was one fatality which involved BZP but on a New Years Eve and it was combined with heroic doses of ecstasy, LSD and again mammoth quantities of alcohol. BZP was not considered by the medical examiners on the night to be causative.

It is not completely safe, but then neither is getting out of bed in the morning. It is considered risky to take with ecstasy and/or large amounts of alcohol, but if taken as directed by sensible manufacturers, the risks are lower than many other normal everyday human activities such as a trip to the beach, driving in heavy traffic or a passenger flight in a 747.

The risks are lower than activities such as surgery in a public hospital, a trip to the doctor, or, as our then-Prime Minister suggested young people do instead of taking party pills, a walk in one of our national parks, where poorly experienced trampers freeze to their deaths every year!

Some excellent facts and figures there. It’s just a shame I had to be the one to report them.

Fuck you, George Lamb.

Since my last post about the spice behind Spice (and other smoking mixtures such as Smoke, Serenity Now, K2, Sence, etc), it has been brought to my attention that some initial toxicology testing has been done on the synthetic cannabinoid JWH-018. Before we get down to the details however, here’s some pretty weird background information – the sponsor and provider of these studies wishes to remain anonymous! Unfortunately, this makes the whole thing a lot less credible, but since this is the only information we have right now, let’s hope someone else can verify these things at a later date. So far, one professor (who also wishes to remain anonymous) thinks these are real, but as of yet, no one is willing to put their name down on any kind of formal statement. If you, or anyone you know, has the relevant expertise to look over these studies, please drop me a line!

(Quick Update – A lot of people have been discussing and linking to this post, but there remains some suspicion that I have something to gain by saying the JWH-018 isn’t that harmful. Firstly, JWH-018 is now illegal in the UK. Secondly, as I mentioned just above this, if I have got anything wrong, please pick me up on it! If it turns out my analysis of the data is incorrect, I will correct it!)

Feel free to invent your own conspiracy theories, but for now, let’s take a look at the data. You can download the PDF documents in this Zip file [2.04 MB]

CYP450 Inhibition Assay

This first assay looks at the effect of a drug on specific enzymes in your liver. These Cytochrome P450 enzymes are responsible for metabolising the vast majority of drugs you might put in your body, so if you’ve got too much of one drug in your system (ie paracetamol/acetaminophen), then other drugs that are also metabolised by these enzymes (ie alcohol) may compete for these enzymes and so hang around in your system for longer. As you can imagine, it’s important to understand how one drug may affect the metabolism of another, in case of any disasterous drug-drug interactions.

Results: JWH-018 will probably interact with the metabolism of other drugs, so more in vivo work is necessary.

hERG Binding Assay

hERG stands for human Ether-à-go-go Related Gene. This gene codes for a particular type of potassium channel found on heart tissue. This channel pumps potassium ions out of the heart muscle cells and are critical in coordinating the heart’s electrical activity. Unfortunately, these channels are a prime target for drugs to bind to, disrupting their function. This can lead to “Long QT Syndrome”, associated with fainting and can lead to sudden death, so you can see why these kinds of tests are important. Here’s a typical ECG recording showing what’s called the “QT interval” shown in blue, which lasts for longer than it should do if these channels are disrupted.

Results: JWH-018 does not interfere with these channels. That’s a good thing.

Cytotoxicity Assay

This simple test essentially looks at how many cells die when you perfuse them with a drug. The more cells that die, the more toxic the drug.

Results: JWH-018 is not cytotoxic at low concentrations.

GreenScreen HC Genotoxicity Assay

This assay looks at how much a drug will interfere with our DNA. Typically, anything that damages DNA is bad news, being potentially carcinogenic, making the rationale behind this test glaringly obvious. This test was also performed in the presence of a fraction taken from liver cells, which will break down the drug. This not only checks if the drug will damage DNA, but also its breakdown products.

Results: JWH-018 does not damage DNA, so shouldn’t give you cancer.

Rat Repeat Toxicity Assay

Guess what happens in this experiment. A number of renagade lab rats looking for a bad time are rounded up and promised free drugs (kind of like Pleasure Island from Pinocchio; that shit was scary!). The rats are then dosed up and observed. Initially, they appear lethargic (read: totally baked) but a few of them died at higher doses. This appears to be down to problems breathing rather than organ toxicity, but only affected the male rats, who appeared more sensitive to the compound. The drug didn’t appear to accumulate in their systems either, but they did lose some weight, probably because they couldn’t be arsed to eat. JWH-018 showed a huge potency and was found to be tachyphylactic (my new favourite word – it means that more of a drug is required to reach the same state following an initial dosage).

Results: According to FDA guidelines, the human equivalent dose is 0.016 mg/kg but it should be tested in other species before this can be seen as reliable!

Rat Pharmacokinetics

Data is collected on a number of different “pharmacokinetic” aspects of the drug, such as how it is absorbed, distributed throughout the body, metabolised and excreted, which can help with the design of future clinical trials.

Results: JWH-018 is distributed well throughout the rat’s tissues. Metabolism and excretion are normal, with a plasma half-life of approximately 2 hours

Summary

Well, from the looks of these tests, JWH-018 seems to be pretty safe, but unless you want to piss off Ben Goldacre, it would be wise not to rely on this “test tube data” entirely. Also, like I said before, we don’t know where this data has come from, clouding the issue even further.

Feel free to ask any questions in the comments.

Big thanks to Alfa @ Drugs-Forum.com for letting me know about these studies. You can read all about JWH-018 on their Drugs Wiki.

COMMENTS IN THIS THREAD ARE NOW CLOSED. YOU CAN CONTINUE DISCUSSING SYNTHETIC CANNABINOIDS HERE OR INDIVIDUAL SMOKING MIXTURES HERE.

The Spice smoking mixture range has been one of the most popular “herbal” smokes ever, and now it’s no suprise why.

To get an idea of just how popular these mixtures are, just take a look at this data from Google’s keyword tool:

That’s over 37,000 searches a month for these three search terms alone – Spice is definitely a customer favourite. I also get no less than 500 emails a day from Russia asking if I can ship it there by the kilo. So what’s behind it all?

This paper [PDF; 246 kB] has some interesting things to say. It turns out that the Spice blends all contain JWH-018 as well as two compounds based on CP 47497 – all of them synthetic cannabinoids. These are man made chemicals designed to tickle the same receptors as THC, the active compound in cannabis, so it’s no wonder these smoking mixtures are so powerful. The difference in potency between the Spice blends appears to be accounted for by increasing levels of these CP 47497 homologues.

Since this discovery, Spice has been banned in several countries, including Austria and Germany. The BBC also reported on it and had the following to say:

The UK drugs regulator, the Medicine and Healthcare products Regulatory Agency (MHRA), is understood to have identified JWH018 in products available in the UK. It is currently in order to determine whether or not it should be classified as a medicinal product – which would mean it should only be available from a doctor.

The UK Advisory Council on the Misuse of Drugs, which advises the government on whether a drug should be made illegal, is also aware of the substance, and is investigating it.

The Spice manufacturers make no mention of these synthetics on their packaging, so a lot of herb-enthusiasts feel somewhat betrayed. Rightly so, I suppose – not being told just what you’re smoking exactly. People have the choice to put things in their body and some Spice smokers might make a different decision if they had all the facts in hand.

But, why?

The typical reaction to this news seems to be the disgust about putting any of these “unsafe” man-made compounds into their body, as though mother nature was some kind of safety net. “These plants have thousands of years of safe use”, they say! But let’s take a closer look…

Take Kratom, for instance. Kratom contains a powerful compound called mitragynine, which acts upon the opioid receptors; the same targets for opium and its derivatives. One alkaloid in kratom, although present in much smaller quantities, is 7-hydroxymitragynine, which is apparently 17x more potent than morphine! While I wouldn’t call this plant harmful, compared to other drugs like cocaine and heroin, it wouldn’t say it was harmless either. The opioid receptors are a dangerous set of receptors to be messing with – the mu subtype responsible for the classic euphoria that accompanies opiate use also stops you breathing if you tickle them too much. Opiates are also addictive, just like kratom can be if you take too much. While this plant may have seen thousands of years of responsible, moderate use, this is no reassurance at all towards its safety.

Now days, people generally don’t toil in the field every day that Newton sends – we have more free time and money to spend than ever before. We can now afford to use large quantities of kratom every day, as well as other entheogens from around the world, but we don’t have any information about this level of exposure to kratom itself or in combination with other stuff. For all we know, taking a mixture of kratom and Salvia divinorum daily could make your eyeballs explode after day 300, or chronic kratom use might give you some kind of evil superpower. Looking at paracetamol as a rather boring example, if you take the odd one every now and then, you’ll be fine, but if you take 8 pills a day every day for a year, you’ll likely end up with some serious condition. There’s also the fact that modern chemistry can create powerful extracts of these entheogens. Who’s to say they’re safe, just because they come from a plant? And what about any other drugs we might be on? Being on a selective serotonin reuptake inhibitor like Prozac for depression isn’t uncommon in today’s society – combine them with the “perfectly safe” Banisteriopsis caapi vine, itself a monoamine oxidase inhibitor, and you have a potentially fatal combination of drugs in your system. I bet there are many more contraindications we haven’t even considered.

What about plants like cannabis and tobacco? They’ve also been used responsibly for thousands of years, but it’s only when so many people start to take these things that we realised “Actually, smoking is bad for us”. Besides, our current medical knowledge means we’ve only recently been able to diagnose these kind of things. I’m not sure I want to trust any data from a period when epilepsy might have been down to a demonic possession. How many adverse health effects could we identify in these ancient entheogen users based on what we know today?

So, while we can be uncertain of the long term effects on health of JWH-018 and friends, it seems we can’t actually be certain about the safety of most of the things we happily consume. Yes, they may turn out to be super toxic (although probably not, if they’re given to lab rats), but at least they only act on your cannabinoid receptors. Kratom tends to be prepared as a tea – once you’ve drunk it, you’ve drunk it. If you’ve taken too much, you’ll realise when its already in your blood. It would be much harder to overdose on these synthetics due to the speed at which they get in your system – if you’re too stoned, you won’t want to smoke any more, never mind being physically able to. The cannabinoid receptors they target are also much safter than the opioid targets of kratom. Cannabinoid receptors seem play a modulatory role, rather than being majorly important, so messing with them doesn’t have as drastic an effect. Smoking too much might make you feel a bit sick and dizzy for a while, but you certainly won’t stop breathing.

In all, I think Spice is in the wrong for not making this clear in the first place, but then I’m not suprised they didn’t want to list these compounds in the current political climate. Maybe when the government realises that it is our right to put things into our own bodies, listing these ingredients wouldn’t be an issue.

Even with this new information however, I’ll still be using the stuff. It’s great!